708–709 of this issue Risk of Becoming Lost to Follow-up During Active Surveillance for Prostate Cancer Kevin B.. We sought to determine rates of patients becoming lost to follow-up LTFU
Trang 1Platinum Priority – Brief Correspondence – Editor’s Choice
Editorial by Adam B Weiner, Edward M Schaeffer and Scott E Eggener on pp 708–709 of this issue
Risk of Becoming Lost to Follow-up During Active Surveillance for Prostate Cancer
Kevin B Ginsburga, Gregory B Auffenbergb[7_TD$DIFF], c, Ji Qib, Isaac J Powella[8_TD$DIFF] , Susan [9_TD$DIFF] M Linsellb,
James E Montieb[10_TD$DIFF] , David [11_TD$DIFF] C Millerb, Michael L Chera,*
a Department of Urology, Wayne State University, School of Medicine, Detroit, MI, USA; b Department of Urology, University of Michigan, School of Medicine, Ann Arbor, MI, USA; c Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
As the name implies, active surveillance (AS) is a dynamic
process requiring periodic monitoring for disease
progression using tests such as digital rectal exam, serum
prostate-specific antigen (PSA), prostate imaging, and prostate biopsy [1] Despite the general success of this strategy, it is increasingly clear that a small proportion of
a v a i l a b l e a t w w w s c i e n c e d i r e c t c o m
j o u r n a l h o m e p a g e : w w w e u r o p e a n u r o l o g y c o m
Article info
Article history:
Accepted August 9, 2018
Associate Editor:
Matthew Cooperberg
Keywords:
Active surveillance
Prostate cancer
Quality improvement
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Abstract
Active surveillance (AS) has emerged as the preferred management strategy for many men with prostate cancer (PC); however, insufficient longitudinal monitoring may increase the risk of poor outcomes We sought to determine rates of patients becoming lost to follow-up (LTFU) and associated risk factors in a large AS cohort The Michigan Urologic Surgery Improvement Collaborative (MUSIC) maintains a prospective registry
of PC patients from 44 academic and community urology practices Over a 6-yr period (2011–2017), we identified patients managed with AS LTFU was defined as any 18-mo period where no pertinent surveillance testing was entered in the registry With a median surveillance period of 32 mo, the estimated 2-yr LTFU-free probability
calculat-ed by Kaplan-Meier method was [12_TD$DIFF]90% (95% confidence interval [CI] = [13_TD$DIFF]89–[14_TD$DIFF]92%) Both African American race (hazard ratio [HR]: 2.77, 95% CI = 1.81–4.24) and Charlson comorbidity index 1 (HR: 1.55, 95% CI = 1.08–2.23) were independently associated with increased risk of LTFU There was variability in rates of estimated 2-yr LTFU-free survival across MUSIC practices, ranging from 52% (95% CI = 21–100%) to 99% (95%
CI = 97–100%), with a median of 96% (interquartile range: 94–98%), although this did not reach statistical significance (p = 0.076) These data reveal opportunities for urology practices to identify systems to reduce rates of LTFU and improve the long-term safety of AS
Patient summary: [2_TD$DIFF]With a median observation period of 32 mo[3_TD$DIFF], an estimated 10% of patients will be lost to follow-up[15_TD$DIFF]at [16_TD$DIFF]the 2 yr[17_TD$DIFF] time point while on AS African American men and generally unhealthy patients were at increased risk, and there was variability from one urology practice to another There is ample opportunity to improve the quality
of the performance of AS
© 2018 European Association of Urology Published by Elsevier B.V All rights reserved
* Corresponding author Department of Urology, Wayne State University School of Medicine, University Health Center, 4201 St Antoine, Ste 7-C, Detroit, MI 48201, USA Tel +1 313 577 5222; Fax: +1 313 577 5217.
E-mail address: mcher@med.wayne.edu ( Cher).
https://doi.org/10.1016/j.eururo.2018.08.010
Trang 2patients choosing to avoid initial curative treatment will
ultimately miss their window of curability, develop
metastasis, and die of prostate cancer (PC)[2,3]
Urology practices should institute monitoring with
sufficient frequency and rigor to avoid these failures; this
is a facet of AS that is beginning to be explored [4] An
extension of these types of studies is to examine the
frequency with which patients have no follow-up data at all,
a situation called[5_TD$DIFF] “lost to follow-up (LTFU)” Herein, we
sought to define the proportion and characteristics of
patients who initially chose AS but were subsequently no
longer followed, and therefore, LTFU
The Michigan Urological Surgery Improvement
Collabo-rative (MUSIC) maintains a prospective registry of PC patients
from 44 academic and community urology practices within
the state of Michigan Patients were included in this study if
the managing physician indicated AS as the management
strategy in the primary medical record We defined LTFU as a
period of at least 18 mo without any surveillance testing (PSA,
PC imaging, or prostate biopsy) entered into the registry or
the primary medical record The date of the LTFU event was
defined as the date of the last surveillance test entered into
the registry The surveillance period was defined as the start
of AS to the date of data analysis Patients had to have at least
18 potential months of surveillance to be included To
confirm that patients were truly LTFU, trained data
abstrac-tors at each clinical site re-reviewed the primary medical
record of every patient with[18_TD$DIFF]a LTFU event to confirm lack of
clinical data not only in the registry but also in the primary
medical record The MUSIC Coordinating Center also
searched across the registry for duplicate names, birth dates,
and dates of diagnosis to determine if patients LTFU in one
MUSIC practice were being followed by another Further
investigative efforts were made by two large urology
practices to contact every LTFU patient and/or their family
by telephone
From 2011 to 2017, 2211 men met the inclusion criteria Median age for the cohort was 66.2 yr (interquartile range [IQR]: 60.7–71.0; Supplementary Table 1) The median surveillance period[19_TD$DIFF] for the entire cohort was 32.1 mo (IQR: 24.3–43.1) For the 1994 patients without LTFU, the median time[20_TD$DIFF] from the initiation of surveillance to their [21_TD$DIFF]most recent surveillance test was 22.2 mo (IQR: 15.3–32.5) During the study period, 217 patients were LTFU, with an estimated
2-yr LTFU-free probability calculated by Kaplan-Meier
meth-od of 90% (95% confidence interval [CI] = 89–92%; Fig 1) Both African American (AA) race (hazard ratio [HR]: 2.77, 95% CI = 1.81–4.24) and Charlson comorbidity index (CCI)
1 (HR: 1.55, 95% CI = 1.08–2.23) were independently associated with increased risk of LTFU by cox regression modeling (Table 1) Values regarding men with LTFU and Gleason Score, age, PSA, greatest percent cancer involve-ment in individual cores, number of positive cores, or annual AS patient volume per practice or per urologist can
be found in Supplementary Table 1
Most (79/217) LTFU events occurred shortly after enrollment on AS, with fewer events per month thereafter (Supplementary Fig 1) When patients had more than five surveillance tests entered into the registry, only 1.9% were LTFU compared with 6.9% for three to five tests and 26% for none to two tests
After adjusting for age, PSA, Gleason score, race, and CCI, we noted variability in the calculated 2-yr LTFU-free survival among MUSIC practices, ranging from 52% (95% CI = 21–100%)
to 99% (95% CI = 97–100%), with a median of 96% (IQR: 94– 98%), although these differences between practices did not reach conventional statistical significance (p = 0.076;Fig 2) Although a patient may be LTFU within the MUSIC registry, he may be receiving oncologic care elsewhere, and therefore not LTFU from the perspective of the patient To investigate this possibility, we repeatedly attempted to contact 42 LTFU patients and/or their families from two
Fig 1 – Kaplan-Meier curve of[1_TD$DIFF] lost to follow-up[6_TD$DIFF] free survival.
Trang 3large practices using every available phone number,
including emergency contact information We successfully
contacted or confirmed information on 22 (52%), of which
16 (73%) were confirmed to have no oncologic care Three
(14%) had oncologic care outside of MUSIC practices (all by
urologists/none by radiation oncology or medical oncology)
and three (14%) were registry errors (duplication in the
registry or incorrect entries) These data suggest that LTFU
estimates obtained from the MUSIC registry may
overesti-mate LTFU rates from the patient perspective to a small
degree
Although AS is safe for most men, metastasis and death
still occur[2,3] Patients who are LTFU, theoretically, may
have worse outcomes due to insufficient monitoring and missed opportunities to convert to definitive therapy During a median surveillance period of 32 mo, we found that approximately 10% of patients will become LTFU when
on AS for 2 yr Most LTFU events seem to be early in the monitoring period, as indicated by a large number of patients LTFU immediately after being placed on surveil-lance However, LTFU events persisted throughout the length of the study, consistent with the notion that patients remain at risk indefinitely
Osterberg et al.[5]reported that at a safety-net hospital, 17% of patients (n = 104) were LTFU during a 10-yr study period Kraus et al.[6]reported that 50% of patients were LTFU within the first 2 yr at their safety-net hospital compared with 16% at a neighboring cancer center These findings, in concert with the findings of our study, provide a focus for intervention and quality improvement among urology practices to increase compliance with surveillance regimens
There is concern that AA patients have more aggressive
PC, increased risk of progression, and worse PC outcomes
[7–9] Race, socioeconomic status, and education have been shown to affect outcomes and utilization of healthcare in general, as well as cancer care[10,11] The MUSIC registry does not capture potentially confounding factors, such as socioeconomic and educational statuses, that may underlie some of the differences in LTFU rates between AA and Caucasian patients It is important to note that patients of all races, ages, and CCI are at risk for LTFU Our data do not imply that certain patients should be excluded from AS
Table 1 – Multivariable cox regression model on time to lost to
follow-up
Biopsy Gleason score
Race
African American 2.77 (1.81–4.24) <0.001
Charlson comorbidity index
PSA (logarithm) 0.92 (0.76–1.11) 0.4
CI = confidence interval; HR = hazard ratio; PSA = prostate-specific antigen.
Note: Adjusted for practice (hospital) through random effect.
Fig 2 – Practice-level adjusted 2-yr LTFU-free probability based on multivariable cox regression model controlling for age, race, comorbidity, PSA, and biopsy Gleason score Error bars display the 95% confidence interval.
Trang 4However, the data may help identify patients that are at
higher risk for becoming LTFU These concerns can be
relayed to the patient and help the physician and patient
maintain diligent attention to surveillance schedules, with
increased emphasis placed on patients who are at a higher
risk for becoming LTFU, such as AA patients and patients
with CCI1
In summary, we demonstrate that some patients placed
on AS have major gaps in oncologic care These patients are
no longer on AS; instead, they are LTFU and may, therefore,
miss an opportunity for intervention The data we present
reveal opportunities to identify systems of care to reduce
LTFU events, thereby improving the quality and long-term
safety of AS for men with early-stage PC To this end, we
developed a MUSIC“Roadmap” for the management of men
with favorable-risk PC which includes suggested schedules
for AS testing[12] In addition, in 2017, a system was created
within MUSIC to alert participating practices if a patient has
not had clinical information entered into the registry within
19 mo of starting surveillance We are optimistic that this
automated system will increase compliance with
longitu-dinal monitoring and decrease rates of LTFU
Author contributions: Michael L Cher had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Ginsburg, Auffenberg, Cher, Qi.
Acquisition of data: Qi, Linsell.
Analysis and interpretation of data: Ginsburg, Auffenberg, Cher, Qi, Linsell,
Powell, Montie, Miller.
Drafting of the manuscript: Ginsburg, Cher.
Critical revision of the manuscript for important intellectual content:
Ginsburg, Auffenberg, Cher, Qi, Linsell, Powell, Montie, Miller.
Statistical analysis: Qi.
Obtaining funding: Miller, Montie, Linsell.
Administrative, technical, or material support: Qi, Linsell.
Supervision: Powell, Montie, Miller, Cher.
Other: None.
Financial disclosures: Michael L Cher certi fies that all conflicts of
interest, including speci fic financial interests and relationships and
af filiations relevant to the subject matter or materials discussed in the
manuscript (eg, employment/af filiation, grants or funding,
consultan-cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: J.Q., salary
support through MUSIC; S.L., salary support through MUSIC; J.M., salary
support through MUSIC; D.M., salary support through MUSIC.
Funding/Support and role of the sponsor: MUSIC is sponsored by Blue
Cross Blue Shield of Michigan (collection and management of the data).
Acknowledgment: The authors acknowledge the support staff at the MUSIC Coordinating Center, the clinical champions, administrators, data abstractors and urologists at each MUSIC contributing practice (details around speci fic participating urologists and practices can be found at
www.musicurology.com ).
Appendix A Supplementary data Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j eururo.2018.08.010
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